No abstract

There is increasing evidence that chemokines and chemokine receptors are causally involved in tumorigenesis by facilitating tumor proliferation and metastasis. Little is known about the possible function of chemokine receptors in the development and progression of renal cell carcinoma (RCC). We, therefore, analyzed the expression of chemokine receptors in tumor specimens and adjacent healthy kidney tissues [normal kidney cell (NKC)] from 10 RCC patients.We also characterized the permanent RCC cell line A-498. CCR6, CXCR2, and CXCR3 were consistently expressed by both malignant cells and NKCs. A-498 displayed additional expression of CXCR4. Importantly, the expression of CCR3 was almost absent on NKCs but clearly enhanced in a substantial proportion of RCC specimens. The primary CCR3 ligand, eotaxin-1/CCL11, induced intracellular Ca 2+ mobilization, receptor internalization, and proliferation in A-498 cells confirming signaling competence of RCC-associated CCR3. In addition, we screened tumor tissue sections of 219 patients and found that 28% (62 of 219) expressed the CCR3 receptor. The presence of CCR3 in tumor samples seemed to correlate with the grade of malignancy. Previous work has established that eotaxin-1expression is induced by tumor necrosis factor-a, a cytokine known to be present in RCC tissue. Our data, therefore, supports a scenario in which eotaxin-1 as part of tumor-associated inflammation promotes progression and dissemination of CCR3-positive RCC.Cancers of the kidney account for 2% to 3% of all malignancies and have a peak incidence in the fifth and sixth decades of life. Renal cell carcinoma (RCC) is the most common malignant renal tumor with an incidence of 4 to 5 in 100 people. At diagnosis, 20% to 30% of the patients have metastatic disease and even a higher percentage of patients develop metachronous metastases after nephrectomy. When in metastatic progression, systemic therapies of RCC are largely ineffective in impacting disease response or patient survival. Therefore, defining the factors involved in disease progression and metastasis constitutes a necessary approach in the development of effective therapies.Multiple factors are known to contribute to the development and progression of neoplasias in general. Among them, chemokines are increasingly being recognized as key players (for reviews, see refs. 1, 2). Chemokines constitute a family of small (8-10 kDa) secreted proteins that act in paracrine or autocrine fashion. Most chemokines are expressed in response to stimuli [e.g., tumor necrosis factor-a (TNF-a) or IFN-g], but constitutive expression might also occur in a tissue-specific manner. Chemokines exert their activity via interaction with a large family of seven-transmembrane-spanning G protein -coupled receptors (3). There are f20 chemokine receptors described thus far and many of the receptors exhibit widespread binding properties. Thus, several chemokines can signal through the same receptor.Originally, chemokines were discovered as chemoattractants and activators of ...

Renal carcinogenesis is promoted by overexpression of the activated serine/ threonine kinase Akt (p-Akt) and supposedly a concomitant reduction in phosphatase and tensin homologue deleted on chromosome 10 tumour suppressor gene (PTEN), which normally inhibits the activation of Akt. Because promising anti-cancer therapies increasingly focus on pathways involving p-Akt and PTEN, the present study evaluated the expression of p-Akt in renal cell carcinomas and compared it with prognosis. P-Akt and PTEN expression were analysed in a tissue microarray (TMA) from renal cell carcinoma (n ϭ 386) and adjacent uninvolved renal tissue (n ϭ 32) specimens. Increased p-Akt was found more often in the nucleus than in the cytoplasm, and PTEN was concomitantly reduced in about 50% of cases. Neither tumour grade nor stage influenced p-Akt expression, whereas the clear cell and papillary subtypes showed increased

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Fluorescence targeted pelvic lymph node dissection allows for the lymphatic drainage of the prostate to be identified with great reliability. Since only the nodes draining the prostate are removed, the absolute number of removed nodes is decreased while diagnostic accuracy is increased.